Molecular mechanisms of AMPA receptor synapse formation

AMPA受体突触形成的分子机制

• 批准号: 0842724
• 负责人: Elva Diaz
• 金额: $ 36.74万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0842724&HistoricalAwards=false
• 关键词: Molecular; mechanisms; AMPA; receptor; synapse

Brain cells (neurons) transmit electrical information through the central nervous system and elicit specific behaviors through specialized connections called synapses. During development, the intricate and precise pattern of neuronal synapse connections is formed. The goal of this project is to understand the mechanism by which a novel protein (SynDIG1) that was identified in the Principal Investigator's (PI) laboratory functions in synapse development. This study will test the hypothesis that SynDIG1 anchors AMPA-type glutamate receptors (AMPA-Rs) at the postsynaptic compartment via interaction with scaffolding proteins. The researchers will use a combination of approaches including biochemistry, immunocytochemistry, and electrophysiology to address this possibility. While significant progress has been made in the field regarding presynaptic differentiation such as synaptic vesicle clustering and postsynaptic recruitment of scaffolds and NMDA-type glutamate receptors (NMDA-Rs), less is known about the molecules implicated in AMPA-R recruitment during synapse development. Thus, the results of the proposed experiments will fill a major gap in the field of synapse development and function. The broader impacts of the proposed studies include integration of the research and education activities of the PI, specifically in the context of broadening the participation of undergraduate students from underrepresented groups (primarily Hispanic/Latino). The PI is an active participant in various campus programs aimed to increase the number of underrepresented students pursuing postgraduate degrees in science; thus, the PI is in a strong position to recruit such students to the laboratory as members of the research team for this project. Undergraduate participation will be directed by the PI in conjunction with graduate students in the laboratory, thereby integrating research, teaching, and scientific community outreach activities for students pursuing graduate studies in the laboratory.

脑细胞（神经元）通过中枢神经系统传输电信息，并通过称为突触的特殊连接引发特定行为。 在发育过程中，形成了复杂而精确的神经元突触连接模式。 该项目的目标是了解首席研究员 (PI) 实验室发现的一种新型蛋白质 (SynDIG1) 在突触发育中发挥作用的机制。 这项研究将验证 SynDIG1 通过与支架蛋白相互作用将 AMPA 型谷氨酸受体 (AMPA-R) 锚定在突触后区室的假设。 研究人员将结合使用生物化学、免疫细胞化学和电生理学等方法来解决这种可能性。 虽然在突触前分化领域已经取得了重大进展，例如突触小泡聚集以及支架和 NMDA 型谷氨酸受体 (NMDA-R) 的突触后募集，但人们对突触发育过程中与 AMPA-R 募集有关的分子知之甚少。 因此，所提出的实验结果将填补突触发育和功能领域的主要空白。 拟议研究的更广泛影响包括PI的研究和教育活动的整合，特别是在扩大来自代表性不足群体（主要是西班牙裔/拉丁裔）的本科生的参与范围内。 PI 积极参与各种校园项目，旨在增加攻读科学研究生学位的代表性不足的学生数量；因此，PI有能力招募这些学生到实验室作为该项目的研究团队成员。本科生的参与将由 PI 与实验室的研究生共同指导，从而为在实验室攻读研究生的学生整合研究、教学和科学界外展活动。